tbuckley/cabot-search huggingface dataset:
Chemogenetics identifies separate area 25 brain circuits involved in anhedonia and anxiety in marmosets
Authors: Christian M. Wood, Laith Alexander, Johan Alsiö, Andrea M. Santangelo, Lauren McIver, Gemma J. Cockcroft, Angela C. Roberts
Journal: Science Translational Medicine (2023)

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies.
Switching between tofacitinib and baricitinib in alopecia areata: A review of clinical response
Authors: Ahmed Kazmi, Anthony Moussa, Laita Bokhari, Bevin Bhoyrul, Shobha Joseph, Vijaya Chitreddy, Samantha Eisman, Nekma Meah, Rodney Sinclair
Journal: Journal of the American Academy of Dermatology (2023)
Knowledge gaps in fibrotic interstitial lung disease in pan-Asian populations: data not missing at random?
Authors: Felix Chua, Suying Low, Gin Tsen Chai, Yoshikazu Inoue, Voon Ong, Amornpun Wongkarnjana, Kamon Kawkitinarong, Jin Woo Song, Zuhanis Abdul Hamid, Aida Abdul Aziz, Mae Campomanes, Toby M Maher, Philip L Molyneaux, Syazatul Syakirin
Journal: The Lancet Respiratory Medicine (2023)
Integration of Extracellular Matrices into Organ‐on‐Chip Systems
Authors: Hazal Kutluk, Effie E. Bastounis, Iordania Constantinou
Journal: Advanced Healthcare Materials (2023)

The extracellular matrix (ECM) is a complex, dynamic network present within all tissues and organs that not only acts as a mechanical support and anchorage point but can also direct fundamental cell behavior, function, and characteristics. Although the importance of the ECM is well established, the integration of well-controlled ECMs into Organ-on-Chip (OoC) platforms remains challenging and the methods to modulate and assess ECM properties on OoCs remain underdeveloped. In this review, current state-of-the-art design and assessment of in vitro ECM environments is discussed with a focus on their integration into OoCs. Among other things, synthetic and natural hydrogels, as well as polydimethylsiloxane (PDMS) used as substrates, coatings, or cell culture membranes are reviewed in terms of their ability to mimic the native ECM and their accessibility for characterization. The intricate interplay among materials, OoC architecture, and ECM characterization is critically discussed as it significantly complicates the design of ECM-related studies, comparability between works, and reproducibility that can be achieved across research laboratories. Improving the biomimetic nature of OoCs by integrating properly considered ECMs would contribute to their further adoption as replacements for animal models, and precisely tailored ECM properties would promote the use of OoCs in mechanobiology.
The 2022 Annual Report of DataDerm: The database of the American Academy of Dermatology
Authors: Marta Van Beek, Robert A. Swerlick, Toni Kaye, Arik Aninos, Alyssa Burns, Stephanie Bruno, Matthew Fitzgerald, Caryn D. Etkin, Jeffrey P. Jacobs
Journal: Journal of the American Academy of Dermatology (2023)
Human variation impacting MCOLN2 restricts Salmonella Typhi replication by magnesium deprivation
Authors: Kyle D. Gibbs, Liuyang Wang, Zhuo Yang, Caroline E. Anderson, Jeffrey S. Bourgeois, Yanlu Cao, Margaret R. Gaggioli, Martin Biel, Rosa Puertollano, Cheng-Chang Chen, Dennis C. Ko
Journal: Cell Genomics (2023)

Highlights•Cellular GWAS revealed MCOLN2 as an inhibitor of S. Typhi intracellular replication•MCOLN2 acts as an inward rectifying Mg2+ channel on endolysosomes•MCOLN2 deprives S. Typhi of Mg2+ to restrict growth•S. Typhi replication in MCOLN2 knockout cells depends on bacterial PhoPQ signalingSummaryHuman genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like Salmonella enterica serovar Typhi (S. Typhi), the cause of typhoid fever. One key defense during bacterial infection is nutritional immunity: host cells attempt to restrict bacterial replication by denying bacteria access to key nutrients or supplying toxic metabolites. Here, a cellular genome-wide association study of intracellular replication by S. Typhi in nearly a thousand cell lines from around the world—and extensive follow-up using intracellular S. Typhi transcriptomics and manipulation of magnesium availability—demonstrates that the divalent cation channel mucolipin-2 (MCOLN2 or TRPML2) restricts S. Typhi intracellular replication through magnesium deprivation. Mg2+ currents, conducted through MCOLN2 and out of endolysosomes, were measured directly using patch-clamping of the endolysosomal membrane. Our results reveal Mg2+ limitation as a key component of nutritional immunity against S. Typhi and as a source of variable host resistance.Graphical abstract
Human CD34+ hematopoietic stem cell hierarchy: how far are we with its delineation at the most primitive level?
Authors: Fernando Anjos-Afonso, Dominique Bonnet
Journal: Blood (2023)

The ability to isolate and characterize different hematopoietic stem cell (HSC) or progenitor cell populations opens avenues to understand how hematopoiesis is regulated during development, homeostasis, and regeneration as well as in age-related conditions such as clonal hematopoiesis and leukemogenesis. Significant progress has been made in the past few decades in determining the composition of the cell types that exist in this system, but the most significant advances have come from mouse studies. However, recent breakthroughs have made significant strides that have enhanced the resolution of the human primitive hematopoietic compartment. Therefore, we aim to review this subject not only from a historical perspective but also to discuss the progress made in the characterization of the human postnatal CD34+ HSC-enriched populations. This approach will enable us to shed light on the potential future translational applicability of human HSCs.
Treatment effects of soluble guanylate cyclase modulation on diabetic kidney disease at single-cell resolution
Authors: Michael S Balzer, Mira Pavkovic, Julia Frederick, Amin Abedini, Alexius Freyberger, Julia Vienenkötter, Ilka Mathar, Krystyna Siudak, Frank Eitner, Peter Sandner, Manuel Grundmann, Katalin Susztak
Journal: Cell Reports Medicine (2023)

Diabetic kidney disease (DKD) is the most common cause of renal failure. Therapeutics development is hampered by our incomplete understanding of animal models on a cellular level. We show that ZSF1 rats recapitulate human DKD on a phenotypic and transcriptomic level. Tensor decomposition prioritizes proximal tubule (PT) and stroma as phenotype-relevant cell types exhibiting a continuous lineage relationship. As DKD features endothelial dysfunction, oxidative stress, and nitric oxide depletion, soluble guanylate cyclase (sGC) is a promising DKD drug target. sGC expression is specifically enriched in PT and stroma. In ZSF1 rats, pharmacological sGC activation confers considerable benefits over stimulation and is mechanistically related to improved oxidative stress regulation, resulting in enhanced downstream cGMP effects. Finally, we define sGC gene co-expression modules, which allow stratification of human kidney samples by DKD prevalence and disease-relevant measures such as kidney function, proteinuria, and fibrosis, underscoring the relevance of the sGC pathway to patients.
Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study
Authors: Xiaofan Liu, Hu Zhou, Yu Hu, Jie Yin, Junmin Li, Wenming Chen, Ruibin Huang, Yuping Gong, Chengwei Luo, Heng Mei, Bingjie Ding, Chengyuan Gu, Huiping Sun, Yun Leng, Dexiang Ji, Yan Li, Hongyan Yin, Haiyan Shi, Keyan Chen, Jian Wang, Songhua Fan, Weiguo Su, Renchi Yang
Journal: The Lancet Haematology (2023)
GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma
Authors: Francesca Del Bufalo, Biagio De Angelis, Ignazio Caruana, Giada Del Baldo, Maria A. De Ioris, Annalisa Serra, Angela Mastronuzzi, Maria G. Cefalo, Daria Pagliara, Matteo Amicucci, Giuseppina Li Pira, Giovanna Leone, Valentina Bertaina, Matilde Sinibaldi, Stefano Di Cecca, Marika Guercio, Zeinab Abbaszadeh, Laura Iaffaldano, Monica Gunetti, Stefano Iacovelli, Rossana Bugianesi, Stefania Macchia, Mattia Algeri, Pietro Merli, Federica Galaverna, Rachid Abbas, Maria C. Garganese, Maria F. Villani, Giovanna S. Colafati, Federico Bonetti, Marco Rabusin, Katia Perruccio, Veronica Folsi, Concetta Quintarelli, Franco Locatelli
Journal: New England Journal of Medicine (2023)

Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma.In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01).A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×106 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×106 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively.The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT03373097.).
An Alternate Explanation
Authors: Tom Alsaigh, Gurpreet Dhaliwal, Eri Fukaya, Nicholas J. Leeper, Nazish Sayed
Journal: New England Journal of Medicine (2023)

A 48-year-old man with long-standing type 2 diabetes mellitus and chronic kidney disease presented with a 3-month history of numbness, tingling, and faint violaceous discoloration of the tips of multiple fingers and toes.
Nirsevimab for Prevention of RSV in Term and Late-Preterm Infants
Authors: William J Muller, Shabir A Madhi, Beatriz Seoane Nuñez, Manuel Baca Cots, Miroslava Bosheva, Ron Dagan, Laura L Hammitt, Conrado J Llapur, Jose M Novoa, Xavier Saez Llorens, Amy Grenham, Elizabeth J Kelly, Vaishali S Mankad, Manish Shroff, Therese Takas, Amanda Leach, Tonya Villafana
Journal: New England Journal of Medicine (2023)
Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study – A single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines
Authors: Robert H. Shaw, Melanie Greenland, Arabella S.V. Stuart, Parvinder K. Aley, Nick J. Andrews, J. Claire Cameron, Sue Charlton, Elizabeth A. Clutterbuck, Andrea M. Collins, Tom Darton, Tanya Dinesh, Christopher J.A. Duncan, Saul N. Faust, Daniela M. Ferreira, Adam Finn, Anna L. Goodman, Christopher A. Green, Bassam Hallis, Paul T. Heath, Helen Hill, Teresa Lambe, Vincenzo Libri, Patrick J. Lillie, Ella Morey, Yama F. Mujadidi, Ruth Payne, Emma L. Plested, Samuel Provstgaard-Morys, Maheshi N. Ramasamy, Mary Ramsay, Robert C. Read, Hannah Robinson, Gavin R. Screaton, Nisha Singh, David P.J. Turner, Paul J. Turner, Rachel White, Jonathan S. Nguyen-Van-Tam, Xinxue Liu, Matthew D. Snape
Journal: Journal of Infection (2023)
Role of Rituximab Addition to First-line Chemotherapy Regimens in Nodular Lymphocyte-predominant Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi
Authors: Manuel Gotti, Roberta Sciarra, Alessandro Pulsoni, Francesco Merli, Stefano Luminari, Caterina Zerbi, Livio Trentin, Alessandro Re, Chiara Rusconi, Simonetta Viviani, Andrea Rossi, Federica Cocito, Barbara Botto, Erika Meli, Antonello Pinto, Irene Dogliotti, Guido Gini, Benedetta Puccini, Francesca Ricci, Luca Nassi, Alberto Fabbri, Anna Marina Liberati, Michele Merli, Andrea Riccardo Filippi, Maurizio Bonfichi, Valentina Zoboli, Germana Tartaglia, Giorgia Annechini, Gianna Maria D’Elia, Ilaria Del Giudice, Isabel Alvarez, Andrea Visentin, Stefano Pravato, Daniela Dalceggio, Chiara Pagani, Silvia Ferrari, Caterina Cristinelli, Tanja Lazic, Virginia Valeria Ferretti, Umberto Ricardi, Luca Arcaini
Journal: HemaSphere (2023)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5–12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss &gt;10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II–III–IV NLPHL.
Joint Asian Pacific Association of Gastroenterology (APAGE)–Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia
Authors: Francis K L Chan, Martin C S Wong, Andrew T Chan, James E East, Han-Mo Chiu, Govind K Makharia, David Weller, Choon Jin Ooi, Julajak Limsrivilai, Yutaka Saito, Dao V Hang, Jon D Emery, Dadang Makmun, Kaichun Wu, Raja Affendi Raja Ali, Siew C Ng
Journal: Gut (2023)

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE–APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.
Dietary sugar consumption and health: umbrella review
Authors: Yin Huang, Zeyu Chen, Bo Chen, Jinze Li, Xiang Yuan, Jin Li, Wen Wang, Tingting Dai, Hongying Chen, Yan Wang, Ruyi Wang, Puze Wang, Jianbing Guo, Qiang Dong, Chengfei Liu, Qiang Wei, Dehong Cao, Liangren Liu
Journal: BMJ (2023)

Abstract Objective To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes. Design Umbrella review of existing meta-analyses. Data sources PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of reference lists. Inclusion criteria Systematic reviews and meta-analyses of randomised controlled trials, cohort studies, case-control studies, or cross sectional studies that evaluated the effect of dietary sugar consumption on any health outcomes in humans free from acute or chronic diseases. Results The search identified 73 meta-analyses and 83 health outcomes from 8601 unique articles, including 74 unique outcomes in meta-analyses of observational studies and nine unique outcomes in meta-analyses of randomised controlled trials. Significant harmful associations between dietary sugar consumption and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic) were detected. Moderate quality evidence suggested that the highest versus lowest dietary sugar consumption was associated with increased body weight (sugar sweetened beverages) (class IV evidence) and ectopic fatty accumulation (added sugars) (class IV evidence). Low quality evidence indicated that each serving/week increment of sugar sweetened beverage consumption was associated with a 4% higher risk of gout (class III evidence) and each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease (class II evidence) and all cause mortality (class III evidence), respectively. In addition, low quality evidence suggested that every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer (class III evidence). Conclusions High dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week (approximately 200-355 mL/week) are recommended to reduce the adverse effect of sugars on health. Systematic review registration PROSPERO CRD42022300982.
Rhythmic attentional scanning
Authors: Pascal Fries
Journal: Neuron (2023)

Sensory processing, short-term memory, and decision-making often deal with multiple items, or options, simultaneously.I review evidence suggesting that the brain handles such multiple items by ''rhythmic attentional scanning (RAS)'': each item is processed in a separate cycle of the theta rhythm, involving several gamma cycles, to reach an internally consistent representation in the form of a gamma-synchronized neuronal group.Within each theta cycle, items that are extended in representational space are scanned by traveling waves.Such scanning might go across small numbers of simple items linked into a chunk.
RSV Illness in the Young and the Old — The Beginning of the End?
Authors: Ruth A. Karron
Journal: New England Journal of Medicine (2023)

Respiratory syncytial virus (RSV) infection was reported 66 years ago among young children with lower respiratory tract illness who were hospitalized in Baltimore.1 RSV infection has since emerged as the most frequent cause of hospitalization among infants in the United States and as the leading cause of pneumonia in young children worldwide. Among children younger than 5 years of age, RSV is associated with approximately 33 million cases of lower respiratory tract illness, 3.6 million hospital admissions, and more than 100,000 deaths each year.2 Infants younger than 6 months of age are at greatest risk for RSV-associated illness and death, . . .
Colchicine twice a day for hand osteoarthritis (COLOR): a double-blind, randomised, placebo-controlled trial
Authors: Anna Døssing, Marius Henriksen, Karen Ellegaard, Sabrina Mai Nielsen, Lisa K Stamp, Felix C Müller, Margreet Kloppenburg, Ida K Haugen, Geraldine M McCarthy, Philip G Conaghan, Louise Ulff-Møller Dahl, Lene Terslev, Roy D Altman, Fabio Becce, Elisabeth Ginnerup-Nielsen, Lene Jensen, Mikael Boesen, Robin Christensen, Ulla Dal, Henning Bliddal
Journal: The Lancet Rheumatology (2023)